Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569137 | SCV000671900 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-03 | criteria provided, single submitter | clinical testing | The c.890_899del10 pathogenic mutation, located in coding exon 6 of the RAD51C gene, results from a deletion of 10 nucleotides at nucleotide positions 890 to 899, causing a translational frameshift with a predicted alternate stop codon (p.L297Hfs*2). This alteration has been identified in a cohort of 2649 consecutive cases of breast and/or ovarian cancer and in an individual diagnosed with prostate cancer (Golmard L et al. Eur. J. Hum. Genet., 2017 12;25:1345-1353; Paulo P et al. PLoS Genet., 2018 04;14:e1007355). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Labcorp Genetics |
RCV000576176 | SCV000676964 | pathogenic | Fanconi anemia complementation group O | 2024-11-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu297Hisfs*2) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 25980754, 29255180, 29659569). ClinVar contains an entry for this variant (Variation ID: 484744). Studies have shown that this premature translational stop signal is associated with inconclusive levels of altered splicing (internal data). For these reasons, this variant has been classified as Pathogenic. |
Mendelics | RCV000576176 | SCV001140726 | pathogenic | Fanconi anemia complementation group O | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000569137 | SCV001347925 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-01 | criteria provided, single submitter | clinical testing | This variant deletes 10 nucleotides in exon 6 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in one individual each affected with ovarian cancer (PMID: 29255180), breast and ovarian cancer (PMID: 33326660), bladder and prostate cancer (PMID: 29659569) and an individual affected with Lynch syndrome-associated cancer and/or polyps (PMID: 25980754). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Molecular Oncology Research Center, |
RCV000709516 | SCV001438607 | pathogenic | Hereditary breast ovarian cancer syndrome | 2020-08-01 | criteria provided, single submitter | research | |
Sema4, |
RCV000569137 | SCV002530028 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-20 | criteria provided, single submitter | curation | |
Gene |
RCV003314621 | SCV004014214 | pathogenic | not provided | 2023-06-16 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25980754, Monteiro2019[MtgAbstract], 29659569, Cardoso2018[Thesis], 27535533, Teixeira2023[preprint], 33258288, 35264596, 33326660, 29255180, 36119527) |
Baylor Genetics | RCV003459371 | SCV004208015 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2024-03-22 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003459371 | SCV004933029 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2024-01-03 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |